Biomarkers in Patients with Sepsis or Acute Respiratory Distress Syndrome

脓毒症或急性呼吸窘迫综合征患者的生物标志物

• 批准号: 8565326
• 负责人: ANTHONY F. SUFFREDINI
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8565326
• 关键词: ATP phosphohydrolase; Acute; Acute Respiratory Distress Syndrome; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Archives; Autoantibodies; Autoantigens; Biological Assay; Biological Markers; Blood specimen; Bronchoalveolar Lavage; Carboxy-Lyases; Categories; Clinical; Clinical Trials; Coagulation Process; Collaborations; Complication; Diffuse; Enrollment; Etiology; Fever; Functional disorder; Goals; Growth Factor; Healthcare; Hemostatic Agents; Hypotension; Immunoassay; Infection; Inflammation; Inflammatory Response; Injury; Institutional Review Boards; Interleukin-6; Ischemia; Lead; Life; Lung; Measures; Mediating; Mediator of activation protein; Methods; Methylprednisolone; Morbidity - disease rate; Organ; Outcome; Pathogenesis; Patients; Plasma; Play; Pneumonia; Potassium Channel; Protein Array; Protein C; Proteins; Pulmonary aspiration of gastric contents; Research; Respiratory Failure; Role; Rosa; Sampling; Sepsis; Septic Shock; Shock; Site; Stomach; Syndrome; Tachycardia; Technology; Tennessee; Time; Time Study; Tissues; Tumor Necrosis Factor-alpha; Universities; Vascular Endothelial Growth Factors; Vasodilation; Viscera; White Blood Cell Count procedure; base; chemokine; cytokine; high risk; lung injury; microbial; mortality; pathogen; procalcitonin; response; septic; treatment as usual

We are evaluating biomarkers in patients with severe infections that lead to shock and lung dysfunction. Samples are being analyzed in collaboration with collaborators at the University of Tennessee Memphis who have conducted a trial prospectively evaluating the effects of corticosteroids on outcome from septic shock or severe respiratory failure. Our goals are to evaluate biomarkers at the time of study entry and during the course of the illness to determine if there are molecules that will help characterize the patients who are likely to have a beneficial response from corticosteroid therapy. During the last year we have screened samples from patients with documented infection and ARDS for chemokines, cytokines, hemostatic, and growth factors that have been suggested to play a role in the pathogenesis of lung injury. We utilized a highly sensitive antibody profiling technology to study autoantibodies in 48 patients with either acute respiratory distress syndrome (ARDS) or severe sepsis. 57% of ARDS and 46% of septic patients without ARDS had elevated autoantibodies compared to the healthy controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that titers of low autoantibodies at early time points rose precipitously and peaked between days 7-14. The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self-proteins and may contribute to late term sequela of systemic inflammation. We studied biomarkers in 79 patients receiving methylprednisolone or usual care during early ARDS. Interleukin-6, tumor necrosis factor α, vascular endothelial growth factor, protein C, procalcitonin and proadrenomedullin were measured in archived plasma. We found that the changes in biomarkers changes varied with the precipitating cause of ARDS (infectious vs noninfectious and pulmonary vs non-pulmonary etiologies), suggesting that the underlying mechanisms and response to anti-inflammatory therapy may vary with the cause of ARDS.

我们正在评估严重感染的患者的生物标志物，导致休克和肺功能障碍。样本正在与田纳西大学孟菲斯大学的合作者合作进行分析，后者已经进行了试验，该试验前瞻性地评估了皮质类固醇对败血性休克或严重呼吸衰竭结果的影响。我们的目标是在研究进入时和疾病过程中评估生物标志物，以确定是否有分子有助于表征可能对皮质类固醇治疗有益反应的患者。在过去的一年中，我们筛选了来自趋化因子，细胞因子，止血和生长因子的病历和ARDS患者的样品，这些样本被认为在肺部损伤的发病机理中起作用。 我们利用高度敏感的抗体分析技术来研究48例急性呼吸窘迫综合征（ARDS）或严重败血症患者的自身抗体。与健康对照组相比，无需ARD的ARDS和46％的ARDS和46％的自身抗体升高。针对包括钾通道调节剂，胃ATPase，谷氨酸脱羧酶-65和几种细胞因子（包括钾通道调节剂）的频谱检测到频繁的高滴度抗体。对系列样品的分析表明，早期时间点低自身抗体的滴度急剧上升，并在第7-14天之间达到峰值。 ARDS和严重败血症中自身抗体的快速诱导表明，持续的系统性炎症和相关的组织破坏介导了对这些自我蛋白质的耐受性的破裂，并可能导致全身炎症的后期后遗症。 我们研究了79例在早期ARDS期间接受甲基促甲硅龙或经常护理的患者的生物标志物。白介素-6，肿瘤坏死因子α，血管内皮生长因子，蛋白C，降钙素和原肾上腺素蛋白在存档的血浆中测量。我们发现，生物标志物变化的变化随ARD的降水原因而变化（传染性与非感染和肺部与非肺病病因），这表明基本机制和对抗炎疗法的反应可能会随ARDS的原因而变化。